【正文】 ory testing, which is required by the CGMP regulations (167。This guidance applies to laboratory testing during the manufacture of active pharmaceutical ingredients, excipients, and other ponents and the testing of finished products to the extent that current good manufacturing practices (CGMP) regulations apply (21 CFR parts 210 and 211). Specifically, the guidance discusses how to investigate suspect, or OOS test results, including the responsibilities of laboratory personnel, the laboratory phase of the investigation, additional testing that may be necessary, when to expand the investigation outside the laboratory, and the final evaluation of all test results.本指南適用于API、賦形劑和其它組分生產(chǎn)的實驗室檢驗和CGMP法規(guī)應(yīng)用的成品檢驗。如果其他可選擇的相接近的指南能滿足適用的法令和法規(guī)的要求，也可以使用。關(guān)于藥品檢驗結(jié)果OOS的調(diào)查作者：日期：Guidance for Industry，Investigating Out of Specification(OOS) Test Results for Pharmaceutical Production行業(yè)指南：藥品檢驗結(jié)果OOS的調(diào)查DRAFT GUIDANCE指南草案. Department of Health and Human ServicesFood and Drug AdministrationCenter for Drug Evaluation and Research (CDER)September 1998CP TABLE OF CONTENTS目錄I. INTRODUCTION 序言. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . .. . . . .. . . .. . . 1II. BACKGROUND . 背景. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . 1III. IDENTIFYING AND ASSESSING OOS TEST RESULTS OOS檢驗結(jié)果的判斷和評估. . .. 2A. Responsibility of the Analyst 檢驗員的責(zé)任. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 2B. Responsibilities of the Supervisor主管的責(zé)任. . . . . . . . . . . . . . . .. . . . . .. . . . . . . . . . . . . . . .. . . . .3IV. INVESTIGATING OOS TEST RESULTS OOS 檢驗結(jié)果的調(diào)查. . . . . . . . . . . . . . . . . . . .. 5A. General Investigational Principles . . 一般調(diào)查原則. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5B. Laboratory Phase of an Investigation . 實驗室的調(diào)查階段 . . . . . . . . . . . . . . . .. . . .. . . . . . . . . . . . 6V. CONCLUDING THE INVESTIGATION . .調(diào)查結(jié)論 . . . . . . . . . . . . . . . . . . . . . . . . .. . .. . . . . . . 10A. Interpretation of Investigation Results . 調(diào)查結(jié)果的解釋 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10B. Reporting . . .報告 . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11This guidance has been prepared by the Office of Compliance/Division of Manufacturing and Product Quality, Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration. This guidance document represents the Agency’s current thinking on evaluating OOS test results. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statute, regulations, or both.本指南由FDA的CDER的達(dá)標(biāo)辦公室/制造、產(chǎn)品、質(zhì)量分部起草，本指南闡明了機構(gòu)關(guān)于評估OOS檢驗結(jié)果的現(xiàn)行的想法。它不會創(chuàng)造或贈與任何人任何權(quán)力，也不會約束FDA或公眾。GUIDANCE FOR INDUSTRY1Investigating Out of Specification (OOS) Test Resultsfor Pharmaceutical Production行業(yè)指南：藥品檢驗結(jié)果OOS的調(diào)查I. INTRODUCTION 序言This guidance for industry provides the Agency’s current thinking on how to evaluate suspect, or out of specification (OOS), test results. For purposes of this document, the term OOS results includes all suspect results that fall outside the specifications or acceptance criteria established in new drug applications, official pendia, or by the manufacturer.本行業(yè)指南反應(yīng)了FDA關(guān)于如何評估懷疑的或OOS檢驗結(jié)果的現(xiàn)行想法，本指南的目的，OOS結(jié)果包括超出了新藥申請材料、法定標(biāo)準(zhǔn)、生產(chǎn)商建立的可接受標(biāo)準(zhǔn)或規(guī)格的所有可疑的結(jié)果。特別的，指南討論了如何調(diào)查可疑的或OOS檢驗結(jié)果，包括了實驗室人員的責(zé)任、實驗室階段調(diào)查、必須的額外試驗，何時進行實驗室范圍外的調(diào)查和對所有檢驗結(jié)果的最終評估。 ), is necessary to confirm that ponents, containers and closures, inprocess materials, and finished products conform to specifications, including stability. Testing Specifications must be scientifically sound and appropriate (21 CFR (b)), and test procedures must be validated as to their accuracy, reliability, and suitability under actual conditions of use (21 CFR (a)(2)). For products that are the subjects of NDAs, ANDAs, or INDs, specifications are contained in the application. Specifications for nonapplication products may be found in official pendia, or established by the manufacturer.FDA認(rèn)為在藥品生產(chǎn)中實驗室檢驗和文件記錄的完整性是基本重要的。檢驗標(biāo)準(zhǔn)必須是科學(xué)正確和適當(dāng)?shù)模? CFR (b)，檢驗方法必須驗證現(xiàn)行使用條件下的正確性、線性和適應(yīng)性(21 CFR (a)(2))，如果是用于NDAs, ANDAs, 或 INDs申請的產(chǎn)品，申請材料中應(yīng)包括標(biāo)準(zhǔn)。Although the subject of this document is OOS results, much of the guidance may be useful for examining results that are out of trend. also supports analytical and process validation efforts. General CGMP regulations covering laboratory operations can be found in part 211, subparts I (Laboratory Controls) and J (Records and Reports). These regulations provide for the establishment of scientifically sound and appropriate specifications, standards, and test procedures that are designed to ensure that ponents and containers of drug products conform to the established standards. Section (f) of the CGMP regulations specifies that products that fail to meet established standards and other relevant quality control criteria will be rejected.盡管本指南的目的是OOS結(jié)果，其中許多部分對于調(diào)查超出趨勢以外的結(jié)果也是有用的，對分析和工藝驗證也有用。這些法規(guī)規(guī)定了科學(xué)正確和適當(dāng)?shù)挠糜诒ＷC制劑的成分和容器符合建立標(biāo)準(zhǔn)的規(guī)格、標(biāo)準(zhǔn)和檢驗方法的建立。III. IDENTIFYING AND ASSESSING OOS TEST RESULTS OOS檢驗結(jié)果的判斷和評估FDA regulations require that an investigation be conducted whenever an OOS test result is obtained. The purpose of the investigation is to determine the cause of the OOS. Even if a batch is rejected based on an OOS result, the investigation is necessary to determine if the result is associated with other batches of the same drug product or other products. Batch rejection does not negate the need to perform the investigation. The regulations require that a written record of the investigation be made including the conclusions of the